Paracetamol Half-Life Declines over Time After an Acute Overdose

Background: Paracetamol poisoning is one of the most common types of drug-induced poisoning worldwide and can cause severe hepatotoxicity. Acetylcysteine administration is the most effective intervention to prevent hepatotoxicity. Clinically, we observed multiple cases in which the initially prolonged paracetamol half-life decreased during acetylcysteine treatment. This study aimed to investigate the changes in the half-life of paracetamol in patients with paracetamol poisoning treated with acetylcysteine. Methods: This was a retrospective observational study on patients with paracetamol poisoning who were treated with acetylcysteine. Patients with ≥3 paracetamol plasma concentrations during a single acute overdose were selected from 2 hospitals in the Netherlands. The half-lives of paracetamol in these patients were calculated using consecutive samples. A moderately prolonged paracetamol half-life was defined as a first half-life of >4.0 hours and a severely prolonged paracetamol half-life of >5.5 hours. Results: Seventy-one paracetamol overdoses from 59 patients were included. The half-life of paracetamol changed from 4.6 (3.5–8.2) h for the first half-life to 2.9 (2.1–3.8) hours for the second half-life ( P < 0.001). In 20 cases (28%), the initial half-life was moderately prolonged (4.0–5.5 hours), and in 26 cases (37%), it was severely prolonged (>5.5 hours). In all 3 subgroups, the half-life decreased significantly between the first and second half-lives ( P < 0.001). The reported ingested dose, 4-hour paracetamol concentration, and time to acetylcysteine administration did not differ between the subgroups. Conclusions: Our results suggest that the half-life of paracetamol decreases during acetylcysteine treatment. Health care professionals should consider repeated measurements of paracetamol concentrations and calculation of half-lives when using paracetamol half-life as a marker of hepatotoxicity, particularly when deciding whether to extend acetylcysteine treatment beyond the duration stated in the current guidelines.